A research team at the Roswell Park Cancer Institute in Buffalo found that a previously identified antibiotic has anti-melanoma activity. The study entitled “Pharmacological targeting of guanosine monophosphate synthase suppresses melanoma cell invasion and tumorigenicity” was published in the journal Cell Death and Differentiation. This research was supported by the Jennifer Linscott Tietgen Family Foundation, which is dedicated to supporting melanoma cancer research in memory of their daughter, Jennifer.
Melanoma is one of the most aggressive forms of cancer due to its ability to metastasize and resist conventional anticancer chemotherapy. The development of novel anti-melanoma strategies depends on a better understanding of its aggressiveness. The invasion potential of melanoma cells is based on the production of guanylate, one of the building blocks of RNA, which is an intermediate molecule between genes and its products.
The study reports that the enzyme that drives guanylate production in the cell, guanosine monophosphate synthase (GMPS), is increased in human metastatic melanoma specimens. This led the research team to hypothesize that GMPS is required for melanoma invasion and can be pharmaceutically targeted to control melanoma growth. Once the team identified Angustmycin A as a GMPS inhibitor, they investigated its anti-melanoma efficacy. The results demonstrated that Angustmycin A, known for a long time (as far back as early 1950s) for its anti-bacterial action, inhibits melanoma invasion in vitro and melanoma cell growth in a preclinical animal model. Compared with other anti-cancer drugs, Angustmycin A treatment resulted in a significant reduction of melanoma growth.
“These are early, preclinical findings, but they open up the exciting prospect of possibly treating melanoma with an inexpensive and well-tolerated agent,” said study author Dr. Mikhail Nikiforov in a press release. “And because we have previously shown that guanylate pools can influence the invasion of cell lines derived from other types of cancer as well, we are also excited about the possibility of uncovering widespread mechanisms and targets that can be common to other kinds of tumors,” he added.
The authors suggest that Angustmycin A should be further evaluated as an anti-melanoma drug in clinical settings, namely in combination with conventional therapy.